The interactions and structure of cell membranes play a key role in the understanding of normal and neoplastic cell behavior. Cellular events can be initiated by the binding of ligands such as hormones and lectins to membrane receptors. An understanding of this initial event, ligand binding, provides a pivotal basis for defining mondulating influences on cellular behavior. Experimental data attesting to negative and positive cooperativity on binding, number of receptors, low site occupancy, and ligand binding affinities are currently subject to widely differing interpretations with ligands such as insulin and con A. Correlation with biologic behavior follows. We have shown that at least part of the positive cooperativity of con A binding to erythrocytes depends upon the dissociation of con A at low concentration. This work will be extended to other cells; the utilization of covalently stabilized con A will provide a better interpretation of the number of membrane receptors, binding affinities, positive (and negative) cooperativity. In the latter regard, the number of receptors extrapolated from a Scatchard plot are generally obtained by assigning a single molecular weight to the ligand, yet a multimeric-multivalent ligand may self-dissociate or associate. Under the best of circumstances, distinguishing membrane-dependent from ligand-dependent positive cooperativity of binding could be troublesome. A novel and simple approach is proposed to identify membrane-dependent positive cooperativity.